DESCRIPTION: (Verbatim) - Hyperpigmentary skin disorders affect several millions of people worldwide and are often the cause of social, life style and emotional problems. These disorders include solar lentigines (liver spots), vitiligo, freckles, and darkening of grafted skin. Additionally, the desire for skin whitening cosmetics is common in various cultures around the world. Current treatments lightening skin are usually topically applied harsh chemicals, such as hydroquinone or its derivatives, but overall lack reliability in efficacy and have issues of safety. We have isolated and characterized a unique and potent skin lightening protein from hyperpigmented xenographs. This natural agent provides a new approach to blocking the formation of melanin, the cause of hyperpigmentation. In both in vitro and in vivo models, the protein effectively inhibits the activity of tyrosinase, a marker for hyperpigmentation. A small fragment of the protein has been identified that effectively mimics the in vitro activity. The goals of these Phase I studies are to demonstrate in vivo effectiveness of the fragment and to identify a small series of peptides for optimization and clinical evaluation in Phase II. The effective topical products from Phase II will provide the prototype product for commercialization in Phase III. PROPOSED COMMERCIAL APPLICATION: A topical skin lightening product has significant commercial medical opportunities in the prevention and treatment of skin discoloration disorders and in cosmeceutical use. Burn victims, the aging and other individuals with skin hyperpigmentation exist by the millions throughout the world. This would be a significant market. The cosmeceutical uses expand the potential many fold.